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EXPLORE IDM’S CURRENT RESEARCH PUBLICATIONS

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ARXIV.ORG Q-BIO

Containing the recent West African outbreak of Ebola virus (EBOV) required the deployment of substantial global resources. Operationally, health workers and surveillance teams treated cases, collected genetic samples, and tracked case contacts. Despite the substantial progress in analyzing and modeling EBOV epidemiological data, a complete characterization of the spatiotemporal spread of Ebola cases remains a challenge. In this work, we offer a novel perspective on the EBOV epidemic that utilizes virus genome sequences to inform population-level, spatial models. Calibrated to phylogenetic linkages, these dynamic spatial models provide unique insight into the disease mobility of EBOV in Sierra Leone. Further, we developed a model selection framework that identifies important epidemiological variables influencing the spatiotemporal propagation of EBOV. Consistent with other investigations, our results show that the spread of EBOV during the beginning and middle portions of the epidemic strongly depended on the size of and distance between populations. Our analysis also revealed a substantial decline in the dependence on population size at the end of the epidemic, coinciding with the large-scale intervention campaign: Operation Western Area Surge. More generally, we believe this framework, pairing molecular diagnostics with dynamic models, has the potential to be a powerful forecasting tool along with offering operationally-relevant guidance for surveillance and sampling strategies during an epidemic.

Adam Akullian, Bershteyn, Anna, Jewell, Britta, Camlin, Carol S.

AIDS

Though a wide body of observational and model-based evidence underscores the promise of Universal Test and Treat (UTT) to reduce population-level HIV incidence in high-burden areas of Sub-Saharan Africa (SSA), the only cluster- randomized trial of UTT completed to date, ANRS 12249, did not show a significant reduction in incidence. More UTT trials are currently underway, and some have already exceeded the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90–90–90 targets. Still, even with high test and treat coverage, it is unknown whether ongoing trials will engage populations with the greatest potential for onward transmission to achieve the ambitious goal of reducing new HIV infections by 90% between 2010 and 2013. Ultimately, even strategies that successfully meet or exceed the 90– 90–90 targets will leave up to 27% of people living with HIV/AIDS virally nonsuppressed. The epidemiological profile of the ‘missing 27%’ – including their risk behavior, mobility, and network connectedness – is not well understood and must be better characterized to fully evaluate the effectiveness of UTT.

Zhe Bai, Eurika Kaiser, Joshua L. Proctor, J. Nathan Kutz, Steven L. Brunton

AIAAJ

Dynamic mode decomposition has emerged as a leading technique to identify spatiotemporal coherent structures from high-dimensional data, benefiting from a strong connection to nonlinear dynamical systems via the Koopman operator. In this work, two recent innovations that extend dynamic mode decomposition to systems with actuation and systems with heavily subsampled measurements are integrated and unified. When combined, these methods yield a novel framework for compressive system identification. It is possible to identify a low-order model from limited input–output data and reconstruct the associated full-state dynamic modes with compressed sensing, adding interpretability to the state of the reduced-order model. Moreover, when full-state data are available, it is possible to dramatically accelerate downstream computations by first compressing the data. This unified framework is demonstrated on two model systems, investigating the effects of sensor noise, different types of measurements (e.g., point sensors, Gaussian random projections, etc.), compression ratios, and different choices of actuation (e.g., localized, broadband, etc.). In the first example, this architecture is explored on a test system with known low-rank dynamics and an artificially inflated state dimension. The second example consists of a real-world engineering application given by the fluid flow past a pitching airfoil at low Reynolds number. This example provides a challenging and realistic test case for the proposed method, and results demonstrate that the dominant coherent structures are well characterized despite actuation and heavily subsampled data.

Laina D. Mercer, Rana M. Safdar, Jamal Ahmed, Abdirahman Mahamud, M. Muzaffar Khan, Sue Gerber, Aiden O’Leary, Mike Ryan, Frank Salet, Steve J. Kroiss, Hil Lyons, Alexander Upfill-Brown, and Guillaume Chabot-Couture  

BMC MEDICINE

Background

Pakistan is one of only three countries where poliovirus circulation remains endemic. For the Pakistan Polio Eradication Program, identifying high risk districts is essential to target interventions and allocate limited resources.

Methods

Using a hierarchical Bayesian framework we developed a spatial Poisson hurdle model to jointly model the probability of one or more paralytic polio cases, and the number of cases that would be detected in the event of an outbreak. Rates of underimmunization, routine immunization, and population immunity, as well as seasonality and a history of cases were used to project future risk of cases.

Results

AFP surveillance in Pakistan collected data on 43,301 NPAFP cases between January 2003 and June 2016, with an average annual rate increasing from 4.3 to 11.4 NPAFP per 100,000 children under the age of 5 years from 2003 to 2016. Space–time smoothing models fit to the NPAFP vaccination dose history data indicated that zero dose RI and underimmunized rates (fewer than three doses) are highly heterogeneous across Pakistan (Figs. 1). Both zero dose RI and underimmunization rates were high in most of Punjab, Sindh, and KP provinces, and lowest in the western provinces, Balochistan and FATA.

Conclusions

The risk of poliovirus has decreased dramatically in many of the key reservoir areas in Pakistan. The results of this model have been used to prioritize sub-national areas in Pakistan to receive additional immunization activities, additional monitoring, or other special interventions.

VACCINE

The globally synchronized removal of the attenuated Sabin type 2 strain from the oral polio vaccine (OPV) in April 2016 marked a major change in polio vaccination policy. This change will provide a significant reduction in the burden of vaccine-associated paralytic polio (VAPP), but may increase the risk of circulating vaccine-derived poliovirus (cVDPV2) outbreaks during the transition period. This risk can be monitored by tracking the disappearance of Sabin-like type 2 (SL2) using data from the polio surveillance system. We studied SL2 prevalence in 17 countries in Africa and Asia, from 2010 to 2016 using acute flaccid paralysis surveillance data. We modeled the peak and decay of SL2 prevalence following mass vaccination events using a beta-binomial model for the detection rate, and a Ricker function for the temporal dependence. We found type 2 circulated the longest of all serotypes after a vaccination campaign, but that SL2 prevalence returned to baseline levels in approximately 50 days. Post-cessation model predictions identified 19 anomalous SL2 detections outside of model predictions in Afghanistan, India, Nigeria, Pakistan, and western Africa. Our models established benchmarks for the duration of SL2 detection after OPV2 cessation. As predicted, SL2 detection rates have plummeted, except in Nigeria where OPV2 use continued for some time in response to recent cVDPV2 detections. However, the anomalous SL2 detections suggest specific areas that merit enhanced monitoring for signs of cVDPV2 outbreaks.

BMC MEDICINE

Background

Wild type 2 poliovirus was last observed in 1999. The Sabin-strain oral polio vaccine type 2 (OPV2) was critical to eradication, but it is known to revert to a neurovirulent phenotype, causing vaccine-associated paralytic poliomyelitis. OPV2 is also transmissible and can establish circulating lineages, called circulating vaccine-derived polioviruses (cVDPVs), which can also cause paralytic outbreaks. Thus, in April 2016, OPV2 was removed from immunization activities worldwide. Interrupting transmission of cVDPV2 lineages that survive cessation will require OPV2 in outbreak response, which risks seeding new cVDPVs. This potential cascade of outbreak responses seeding VDPVs, necessitating further outbreak responses, presents a critical risk to the OPV2 cessation effort.

Methods

The EMOD individual-based disease transmission model was used to investigate OPV2 use in outbreak response post-cessation in West African populations. A hypothetical outbreak response in northwest Nigeria is modeled, and a cVDPV2 lineage is considered established if the Sabin strain escapes the response region and continues circulating 9 months post-response. The probability of this event was investigated in a variety of possible scenarios.

Results

Under a broad range of scenarios, the probability that widespread OPV2 use in outbreak response (~2 million doses) establishes new cVDPV2 lineages in this model may exceed 50% as soon as 18 months or as late as 4 years post-cessation.

Conclusions

The risk of a cycle in which outbreak responses seed new cVDPV2 lineages suggests that OPV2 use should be managed carefully as time from cessation increases. It is unclear whether this risk can be mitigated in the long term, as mucosal immunity against type 2 poliovirus declines globally. Therefore, current programmatic strategies should aim to minimize the possibility that continued OPV2 use will be necessary in future years: conducting rapid and aggressive outbreak responses where cVDPV2 lineages are discovered, maintaining high-quality surveillance in all high-risk settings, strengthening the use of the inactivated polio vaccine as a booster in the OPV2-exposed and in routine immunization, and gaining access to currently inaccessible areas of the world to conduct surveillance.

B. M. ALTHOUSE, L. L. HAMMITT, L. GRANT, B. G. WAGNER, R. REID, F. LARZELERE-HINTON, R. WEATHERHOLTZ, K. P. KLUGMAN, G. L. RODGERS, K. L. O'BRIEN and H. HU

EPIDEMIOLOGY AND INFECTION

Identifying the transmission sources and reservoirs of Streptococcus pneumoniae (SP) is a long-standing question for pneumococcal epidemiology, transmission dynamics, and vaccine policy. Here we use serotype to identify SP transmission and examine acquisitions (in the same household, local community, and county, or of unidentified origin) in a longitudinal cohort of children and adults from the Navajo Nation and the White Mountain Apache American Indian Tribes. We found that adults acquire SP relatively more in the household than other age groups, and children 2–8 years old typically acquire in their own or surrounding communities. Age-specific transmission probability matrices show that transmissions within household were mostly seen from older to younger siblings. Outside the household, children most often transmit to other children in the same age group, showing age-assortative mixing behavior. We find toddlers and older children to be most involved in SP transmission and acquisition, indicating their role as key drivers of SP epidemiology. Although infants have high carriage prevalence, they do not play a central role in transmission of SP compared with toddlers and older children. Our results are relevant to inform alternative pneumococcal conjugate vaccine dosing strategies and analytic efforts to inform optimization of vaccine programs, as well as assessing the transmission dynamics of pathogens transmitted by close contact in general.

Diego F. Cuadros, Jingjing Li, Adam J. Branscum, Adam Akullian, Peng Jia, Elizabeth N. Mziray, and Frank Tanser

SCIENTIFIC REPORTS

Under the premise that in a resource-constrained environment such as Sub-Saharan Africa it is not possible to do everything, to everyone, everywhere, detailed geographical knowledge about the HIV epidemic becomes essential to tailor programmatic responses to specific local needs. However, the design and evaluation of national HIV programs often rely on aggregated national level data. Against this background, here we proposed a model to produce high-resolution maps of intranational estimates of HIV prevalence in Kenya, Malawi, Mozambique and Tanzania based on spatial variables. The HIV prevalence maps generated highlight the stark spatial disparities in the epidemic within a country, and localize areas where both the burden and drivers of the HIV epidemic are concentrated. Under an era focused on optimal allocation of evidence-based interventions for populations at greatest risk in areas of greatest HIV burden, as proposed by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United States President’s Emergency Plan for AIDS Relief (PEPFAR), such maps provide essential information that strategically targets geographic areas and populations where resources can achieve the greatest impact.

PROCEEDINGS OF THE 2017 WINTER SIMULATION CONFERENCE

Introduction

In public health, it is critical to have a reasonable understanding of an epidemic disease in order to set pragmatic goals and design highly-impactful and cost-effective interventions. Mathematical models of these epidemiological processes can support decision making by forecasting disease spread in space and time, and by evaluating intervention outcomes many times in-silico before spending valuable resources implementing real-world programs. Recent efforts in computational epidemiology have focused on the design and application of detailed stochastic models that capture physical mechanisms through which disease propagates, along with the statistical fluctuations inherent in complex systems. These stochastic models are readily available, and recent work has focused on applying these models to malaria (Eckhoff et al. 2016, Eckhoff 2013, Marshall et al. 2016, Gerardin et al. 2016), HIV (Bershteyn et al. 2016, Eaton et al. 2015), polio (McCarthy et al. 2016, Grassly et al. 2006), and more.

Simulation

Some types of diseases with permanent immunity, such as measles, mumps and rubella, can be described as Susceptible-Infected-Recovered (SIR) model. In this model each individual can only exist in one of the discrete states such as susceptible (S), infected (I) or permanently recovered (R). We have two transitions in this case. An infected person can infect others with an infection rate, β, and is cured with curing rate, δ. Therefore, the parameters of our model are θ = (β,δ). Our objective, here, is finding a good model for the given epidemic data, i.e. infection rate and curing rate, to investigate the properties of the disease spread. These properties will allow the researchers to learn about the diseases, and thereby enabling them to test competing theories about transmission of disease and to devise better containment strategies.

Dr Mami Taniuchi, PhD, Michael Famulare, PhD, Khalequ Zaman, PhD, Md Jashim Uddin, MSc, Alexander M Upfill-Brown, MSc, Tahmina Ahmed, MSc, Parimalendu Saha, MSc, Rashidul Haque, PhD, Ananda S Bandyopadhyay, MBBS, Prof John F Modlin, MD, James A Platts-Mills, MD, Prof Eric R Houpt, MD, Mohammed Yunus, MBBS, Prof William A Petri Jr, MD

THE LANCET INFECTIOUS DISEASES

Background

Trivalent oral polio vaccine (tOPV) was replaced worldwide from April, 2016, by bivalent types 1 and 3 oral polio vaccine (bOPV) and one dose of inactivated polio vaccine (IPV) where available. The risk of transmission of type 2 poliovirus or Sabin 2 virus on re-introduction or resurgence of type 2 poliovirus after this switch is not understood completely. We aimed to assess the risk of Sabin 2 transmission after a polio vaccination campaign with a monovalent type 2 oral polio vaccine (mOPV2).

Methods

We did an open-label cluster-randomised trial in villages in the Matlab region of Bangladesh. We randomly allocated villages (clusters) to either: tOPV at age 6 weeks, 10 weeks, and 14 weeks; or bOPV at age 6 weeks, 10 weeks, and 14 weeks and either one dose of IPV at age 14 weeks or two doses of IPV at age 14 weeks and 18 weeks. After completion of enrolment, we implemented an mOPV2 vaccination campaign that targeted 40% of children younger than 5 years, regardless of enrolment status. The primary outcome was Sabin 2 incidence in the 10 weeks after the campaign in per-protocol infants who did not receive mOPV2, as assessed by faecal shedding of Sabin 2 by reverse transcriptase quantitative PCR (RT-qPCR). The effect of previous immunity on incidence was also investigated with a dynamical model of poliovirus transmission to observe prevalence and incidence of Sabin 2 virus. This trial is registered at ClinicalTrials.gov, number NCT02477046.

Findings

Between April 30, 2015, and Jan 14, 2016, individuals from 67 villages were enrolled to the study. 22 villages (300 infants) were randomly assigned tOPV, 23 villages (310 infants) were allocated bOPV and one dose of IPV, and 22 villages (329 infants) were assigned bOPV and two doses of IPV. Faecal shedding of Sabin 2 in infants who did not receive the mOPV2 challenge did not differ between children immunised with bOPV and one or two doses of IPV and those who received tOPV (15 of 252 [6%] vs six of 122 [4%]; odds ratio [OR] 1·29, 95% CI 0·45–3·72; p=0·310). However, faecal shedding of Sabin 2 in household contacts was increased significantly with bOPV and one or two doses of IPV compared with tOPV (17 of 751 [2%] vs three of 353 [1%]; OR 3·60, 95% CI 0·82–15·9; p=0·045). Dynamical modelling of within-household incidence showed that immunity in household contacts limited transmission.

Interpretation

In this study, simulating 1 year of tOPV cessation, Sabin 2 transmission was higher in household contacts of mOPV2 recipients in villages receiving bOPV and either one or two doses of IPV, but transmission was not increased in the community as a whole as shown by the non-significant difference in incidence among infants. Dynamical modelling indicates that transmission risk will be higher with more time since cessation.

Funding

Bill & Melinda Gates Foundation.